HPD

Homo sapiens (Human)

NA

PPD

4HPPD family

Oxidoreductase

4-hydroxyphenylpyruvate dioxygenase activity.Metal ion binding.

Tyrosinemia 3 (TYRSN3) [MIM:276710]: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild intellectual disability. {ECO:0000269|PubMed:10942115, ECO:0000269|PubMed:11073718}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hawkinsinuria (HWKS) [MIM:140350]: An inborn error of tyrosine metabolism characterized by failure to thrive, persistent metabolic acidosis, fine and sparse hair, and excretion of the unusual cyclic amino acid metabolite, hawkinsin, in the urine. {ECO:0000269|PubMed:11073718}. The disease is caused by variants affecting the gene represented in this entry.

DB02850; DB00348

NA

1.13.11.27

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Dioxygenase; Disease variant; Endoplasmic reticulum; Golgi apparatus; Intellectual disability; Iron; Membrane; Metal-binding; Oxidoreductase; Phenylalanine catabolism; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Tyrosine catabolism

A

43164.8

376

0.11

32.38

6.73

-1.04

-7.58

FASN

Homo sapiens (Human)

Yeast fatty acid synthase; Fatty-acyl-CoA synthase; Fatty acyl-CoA synthetase enzyme; FAS

NA

Acyltransferase

Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities as an acyl carrier protein.

Glycine encephalopathy 2 (GCE2) [MIM:620398]: A form of glycine encephalopathy, a metabolic disorder characterized by a high concentration of glycine in the body fluids. Affected individuals typically have severe neurological symptoms, including seizure, lethargy, and muscular hypotonia soon after birth. Most of them die within the neonatal period. Atypical cases have later disease onset and less severely affected psychomotor development. {ECO:0000269|PubMed:10873393, ECO:0000269|PubMed:11286506, ECO:0000269|PubMed:16051266, ECO:0000269|PubMed:26371980, ECO:0000269|PubMed:28244183, ECO:0000269|PubMed:8005589, ECO:0000269|PubMed:9600239, ECO:0000269|PubMed:9621520}. The disease is caused by variants affecting the gene represented in this entry.

DB01034; DB01083

Q15848; Q16665; P42858; Q8IV20; Q8TBB1; PRO_0000045603 [Q99IB8]

EC 2.3.1.85

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Fatty acid biosynthesis; Fatty acid metabolism; Hydrolase; Isopeptide bond; Lipid biosynthesis; Lipid metabolism; Lyase; Multifunctional enzyme; NAD; NADP; Oxidoreductase; Phosphopantetheine; Phosphoprotein; Proteomics identification; Pyridoxal phosphate; Reference proteome; S-nitrosylation; Transferase; Ubl conjugation

A

30174.9

275

0.09

43.28

5.92

-5.4

-7.59

CYCS

Homo sapiens (Human)

NA

CYC

Cytochrome c family

Oxidoreductase

Electron transporter, transferring electrons from CoQH2-cytochrome c reductase complex and cytochrome c oxidase complex activity.Heme binding.Metal ion binding.

Thrombocytopenia 4 (THC4) [MIM:612004]: A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. {ECO:0000269|PubMed:18345000}. The disease is caused by variants affecting the gene represented in this entry.

DB11638; DB03317; DB03366; DB01017; DB02110; DB03977; DB03934; DB04249

O14727; P05067; Q6XD76; Q9NSI6-4; Q3SXR2; Q96BR5; Q9UKG9-2; O00303; Q8IZU1; Q3SYB3; P06241; Q8N5Z5; Q6A162; Q1L5Z9; P02750; Q8IYG6; Q6FHY5; A0A0A0MR05; Q9BUL5; Q6ZMI0-5; Q66K80; Q9NTN9-3; P37840; Q13573; Q92797-2; O43829; Q9FKS5

NA

3D-structure; Acetylation; Apoptosis; Direct protein sequencing; Disease variant; Electron transport; Heme; Iron; Metal-binding; Mitochondrion; Phosphoprotein; Proteomics identification; Reference proteome; Respiratory chain; Transport

A,B,C,D

11601.4

104

0.09

12.21

9.61

9.01

-7.59

cumD

Pseudomonas fluorescens

NA

NA

NA

Hydrolase

Hydrolase activity.

Intellectual developmental disorder, autosomal dominant 62 (MRD62) [MIM:618793]: An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD62 is characterized by mild to moderately impaired intellectual development. {ECO:0000269|PubMed:27479843, ECO:0000269|PubMed:29460436}. The disease is caused by variants affecting the gene represented in this entry.

DB03741; DB03793; DB03568; DB02531; DB03750; DB02406; DB03766

NA

NA

3D-structure; Hydrolase

A

30307.9

271

0.1

37.49

5.02

-11.58

-7.58

IAA7

Arabidopsis thaliana (Mouse-ear cress)

NA

AXR2;At3g23050;MXC7.8

Aux/IAA family

Signaling protein

DNA binding transcription factor activity.

LTC4 synthase deficiency is associated with a neurometabolic developmental disorder characterized by muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly. {ECO:0000269|PubMed:10896305, ECO:0000269|PubMed:9820300}.

NA

Q9LW29; Q9C5W9; Q8RYC8; Q94AH6; Q9ZR12; P49677; Q38828; Q38829; Q38830; Q38831; O24407; O24408; O24409; P49678; O24410; Q8LAL2; Q9XFM0; Q38822; Q9M1R4; Q9C5X0; Q9C8Y3; Q39255; Q570C0

NA

3D-structure; Alternative splicing; Auxin signaling pathway; Nucleus; Reference proteome; Repressor; Transcription; Transcription regulation

B,C

65385.2

581

0.09

47.83

7.46

1.23

-7.59

RFK

Homo sapiens (Human)

NA

NA

NA

Transferase

ATP binding.Metal ion binding.Riboflavin kinase activity.

Glutaric aciduria 1 (GA1) [MIM:231670]: An autosomal recessive metabolic disorder characterized by progressive dystonia and athetosis due to gliosis and neuronal loss in the basal ganglia. {ECO:0000269|PubMed:14707522, ECO:0000269|PubMed:18775954, ECO:0000269|PubMed:24973495, ECO:0000269|PubMed:8541831, ECO:0000269|PubMed:8900227, ECO:0000269|PubMed:8900228, ECO:0000269|PubMed:9600243, ECO:0000269|PubMed:9711871}. The disease is caused by variants affecting the gene represented in this entry.

DB03247; DB00140

Q9NXG0-2; P19438; P19438-1

2.7.1.26

3D-structure; ATP-binding; Cytoplasm; Flavoprotein; FMN; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Proteomics identification; Reference proteome; Transferase; Zinc

A

16749.9

147

0.12

41.55

7.09

0.12

-7.58

sch PNP

Schistosoma mansoni (Blood fluke)

sch Purine nucleoside phosphorylase; sch Inosine-guanosine phosphorylase

PNP/MTAP phosphorylase family

NA

The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.

Hemolytic anemia, non-spherocytic, due to glucose phosphate isomerase deficiency (HA-GPID) [MIM:613470]: A form of anemia in which there is no abnormal hemoglobin or spherocytosis. It is caused by glucose phosphate isomerase deficiency. {ECO:0000269|PubMed:28803808, ECO:0000269|PubMed:7989588, ECO:0000269|PubMed:8499925, ECO:0000269|PubMed:8822952, ECO:0000269|PubMed:8822954, ECO:0000269|PubMed:9446754, ECO:0000269|PubMed:9856489}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 2.4.2.1

3D-structure; Glycosyltransferase; Transferase

A,B

61140.6

564

0.06

29.8

7.6

1.82

-7.58

PRDX4

Homo sapiens (Human)

Thioredoxindependent peroxide reductase A0372; Thioredoxin peroxidase AO372; PrxIV; Peroxiredoxin4; Peroxiredoxin IV; PRDX4; Antioxidant enzyme AOE372; AOE372

Peroxiredoxin family, AhpC/Prx1 subfamily

Peroxidases

Probably involved in redox regulation of the cell. Regulates the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation.

May be involved in T-cell exhaustion associated with chronic viral infections such as with human immunodeficiency virus (HIV) and hepatitic C virus (HCV). {ECO:0000269|PubMed:19001139, ECO:0000269|PubMed:19587053}.; DISEASE: T-cell lymphoma, subcutaneous panniculitis-like (SPTCL) [MIM:618398]: An uncommon form of T-cell non-Hodgkin lymphoma, in which cytotoxic CD8+ T-cells infiltrate subcutaneous adipose tissue, and rimming adipocytes in a lace-like pattern. Affected individuals typically present with multiple subcutaneous nodules, systemic B-cell symptoms, and, in a subset of cases, autoimmune disorders, most commonly systemic lupus erythematosus. A subset of patients develop hemophagocytic lymphohistiocytosis. SPTCL transmission pattern is consistent with autosomal recessive inheritance with incomplete penetrance. {ECO:0000269|PubMed:30374066, ECO:0000269|PubMed:30792187, ECO:0000269|Ref.2}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

NA

P54253; P18428; P07237; P30101; Q15084; Q06830; P21731; Q8NBS9

EC 1.11.1.15

3D-structure; Antioxidant; Cytoplasm; Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; Oxidoreductase; Peroxidase; Proteomics identification; Redox-active center; Reference proteome; Signal

A

18846.2

166

0.12

30.43

5.54

-3.89

-7.58

GPR119

Homo sapiens (Human)

GPR119; G-protein coupled receptor 119

G-protein coupled receptor 1 family

GPCR rhodopsin

Receptor for the endogenous fatty-acid ethanolamide oleoylethanolamide (OEA) and lysophosphatidylcholine (LPC). Functions as a glucose-dependent insulinotropic receptor. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Seems to act through a G(s) mediated pathway.

Developmental and epileptic encephalopathy 24 (DEE24) [MIM:615871]: A disease characterized by early-onset seizures, intellectual disability of varying degrees, and behavioral disturbances or autistic features in most individuals. {ECO:0000269|PubMed:24747641, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:30351409}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Generalized epilepsy with febrile seizures plus 10 (GEFSP10) [MIM:618482]: An autosomal dominant neurologic disorder with incomplete penetrance, characterized by variable types of seizures including absence, tonic-clonic, febrile, focal, and eyelid myoclonia. Some patients have normal neurologic development. Others have mild-to-moderate intellectual disability or autism spectrum disorder. {ECO:0000269|PubMed:29936235, ECO:0000269|PubMed:30351409}. The disease is caused by variants affecting the gene represented in this entry.

DB05166

Q12797-6

NA

3D-structure; Cell membrane; G-protein coupled receptor; Lipid-binding; Membrane; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

R

32134.1

292

0.12

34.96

9.12

8.03

-7.58

GSTA4

Homo sapiens (Human)

NA

NA

GST superfamily, Alpha family

Transferase

Glutathione transferase activity.Identical protein binding.Protein homodimerization activity.

Cocoon syndrome (COCOS) [MIM:613630]: A lethal syndrome characterized by multiple fetal malformations including defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin. {ECO:0000269|PubMed:20961246}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Bartsocas-Papas syndrome 2 (BPS2) [MIM:619339]: An autosomal recessive, severe form of popliteal pterygium syndrome. Popliteal pterygia syndromes have considerable variability in severity and in the associated phenotypic features but they are all characterized by cutaneous webbing across one or more major joints, cleft lip and/or palate, syndactyly, and genital malformations. {ECO:0000269|PubMed:25691407}. The disease may be caused by variants affecting the gene represented in this entry.

DB00143

Q96LR7; O95995; P09210; O15217; O15116; Q96HA8

2.5.1.18

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Proteomics identification; Reference proteome; Transferase

A,B,C,D

50705.7

438

0.1

50.22

7.95

1.91

-7.57

SDS

Homo sapiens (Human)

NA

SDH

Serine/threonine dehydratase family

Lyase

L-serine ammonia-lyase activity.L-threonine ammonia-lyase activity.Protein homodimerization activity.Pyridoxal phosphate binding.

Immunodeficiency, common variable, 12, with autoimmunity (CVID12) [MIM:616576]: A primary immunodeficiency characterized by hypogammaglobulinemia and recurrent bacterial infections. About half of patients develop autoimmune features, including cytopenia, as well as generalized inflammation and lymphoproliferation manifest as lymphadenopathy or hepatosplenomegaly. {ECO:0000269|PubMed:26279205}. The disease is caused by variants affecting the gene represented in this entry.

DB00114; DB00133

Q8WTU0; O14964; Q96PF1

4.3.1.17; 4.3.1.19

3D-structure; Cytoplasm; Direct protein sequencing; Gluconeogenesis; Lipid metabolism; Lyase; Proteomics identification; Pyridoxal phosphate; Reference proteome

A

33559.7

319

0.06

34.65

7.2

0.42

-7.57

NNMT

Homo sapiens (Human)

NA

NA

Class I-like SAM-binding methyltransferase superfamily, NNMT/PNMT/TEMT family

Transferase

Nicotinamide N-methyltransferase activity.Pyridine N-methyltransferase activity.

Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer. {ECO:0000269|PubMed:10394368}.; DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:9753710}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Lipodystrophy, familial partial, 3 (FPLD3) [MIM:604367]: A form of lipodystrophy characterized by marked loss of subcutaneous fat from the extremities. Facial adipose tissue may be increased, decreased or normal. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia. {ECO:0000269|PubMed:11788685, ECO:0000269|PubMed:12453919}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Glioma 1 (GLM1) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:10851250}. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.

DB00627

NA

2.1.1.1

3D-structure; Acetylation; Citrullination; Cytoplasm; Direct protein sequencing; Methyltransferase; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Transferase

A,B,C,D

27886.8

251

0.1

40.66

5.23

-5.11

-7.57

glf

Escherichia coli (strain K12)

NA

b2036;JW2021;yefE

UDP-galactopyranose/dTDP-fucopyranose mutase family

Isomerase

Flavin adenine dinucleotide binding.UDP-galactopyranose mutase activity.

Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer. {ECO:0000269|PubMed:10394368}.; DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:9753710}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Lipodystrophy, familial partial, 3 (FPLD3) [MIM:604367]: A form of lipodystrophy characterized by marked loss of subcutaneous fat from the extremities. Facial adipose tissue may be increased, decreased or normal. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia. {ECO:0000269|PubMed:11788685, ECO:0000269|PubMed:12453919}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Glioma 1 (GLM1) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:10851250}. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.

DB03147

P11868

5.4.99.9

3D-structure; Direct protein sequencing; FAD; Flavoprotein; Isomerase; Lipopolysaccharide biosynthesis; Reference proteome

A,B

42965.3

367

0.14

32.48

6.62

-1.52

-7.57

CASP2

Homo sapiens (Human)

Protease ICH1; Protease ICH-1; Neural precursor cell expressed developmentally downregulated protein 2; Neural precursor cell expressed developmentally down-regulated protein 2; NEDD2; NEDD-2; ICH1; C

Peptidase C14A family

Peptidase

Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival. Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress. Involved in the activation cascade of caspases responsible for apoptosis execution.

Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly (MRT80) [MIM:620653]: An autosomal recessive disorder characterized by global developmental delay, mildly to moderately impaired intellectual development, attention deficit-hyperactivity disorder, hypotonia, seizure, poor social skills, and autistic traits. Brain imaging shows fronto-temporal lissencephaly and pachygyria. {ECO:0000269|PubMed:37880421}. The disease is caused by variants affecting the gene represented in this entry.

NA

O95429; P42575; P42575-1; P78560; O43741

EC 3.4.22.55

3D-structure; Acetylation; Alternative splicing; Apoptosis; Disease variant; Hydrolase; Intellectual disability; Lissencephaly; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Thiol protease; Zymogen

A,B

28799.4

250

0.08

48.18

5.25

-7.91

-7.57

ARRB1

Homo sapiens (Human)

Non-visual arrestin-2; Betaarrestin1; Arrestin beta1; Arrestin beta-1; ARR1

Arrestin family

Arrestin protein

During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Involved in internalization of P2RY4 and UTP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 ands subsequent recycling. Involved in the degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-activated receptors. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2). ERK1/2 activated by the beta-arrestin scaffold is largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Recruits c-Src/SRC to ADRB2 resulting in ERK activation. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Is required for SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized NK1R resulting in ERK1/2 activation, which is required for the antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-mediated ERK activity. Acts as signaling scaffold for the AKT1 pathway. Is involved in alpha-thrombin-stimulated AKT1 signaling. Is involved in IGF1-stimulated AKT1 signaling leading to increased protection from apoptosis. Involved in activation of the p38 MAPK signaling pathway and in actin bundle formation. Involved in F2RL1-mediated cytoskeletal rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber formation by acting together with GNAQ to activate RHOA. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. May serve as nuclear messenger for GPCRs. Involved in OPRD1-stimulated transcriptional regulation by translocating to CDKN1B and FOS promoter regions and recruiting EP300 resulting in acetylation of histone H4. Involved in regulation of LEF1 transcriptional activity via interaction with DVL1 and/or DVL2 Also involved in regulation of receptors other than GPCRs. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Binds phosphoinositides. Binds inositolhexakisphosphate (InsP6). Involved in IL8-mediated granule release in neutrophils. Required for atypical chemokine receptor ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. Involved in the internalization of the atypical chemokine receptor ACKR3. Negatively regulates the NOTCH signaling pathway by mediating the ubiquitination and degradation of NOTCH1 by ITCH. Participates to the recruitment of the ubiquitin-protein ligase to the receptor. Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes.

Intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP) [MIM:617333]: An autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, delayed language, and facial dysmorphisms, most notably ptosis. Additional features may include poor growth, hypotonia, and seizures. {ECO:0000269|PubMed:27939639, ECO:0000269|PubMed:27939640}. The disease is caused by variants affecting the gene represented in this entry.

NA

P63010-2; O15169; P0DP25; P20963; P25101; P50148; Q5JWF2; Q14749; P06396; Q16665; P11142; Q99683; P53779; P45984; Q00987; P19338; Q14978; P14618; P14859-6; P35813; O75688; Q13523; P06702; P12931; Q15208; Q13428; P04637; P27348; P25490; O43298; O95218; Q7DB77

NA

3D-structure; Alternative splicing; Cell membrane; Cell projection; Coated pit; Cytoplasm; Cytoplasmic vesicle; Membrane; Nucleus; Phosphoprotein; Protein transport; Proteomics identification; Reference proteome; Signal transduction inhibitor; Transcription; Transcription regulation; Transport; Ubl conjugation

A

32455.6

293

0.12

28.99

9.12

9.86

-7.57

NAMPT

Homo sapiens (Human)

Visfatin; PreBcell colonyenhancing factor 1; PreB cellenhancing factor; Pre-B-cell colony-enhancing factor 1; Pre-B cell-enhancing factor; PBEF1; PBEF; Nampt; NAmPRTase

NAPRTase family

Glycosyltransferases

It is the rate limiting component in the mammalian NAD biosynthesis pathway. The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation of clock target gene expression by releasing the core clock component: CLOCK-ARNTL/BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression. Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD.

Hemolytic anemia, non-spherocytic, due to glucose phosphate isomerase deficiency (HA-GPID) [MIM:613470]: A form of anemia in which there is no abnormal hemoglobin or spherocytosis. It is caused by glucose phosphate isomerase deficiency. {ECO:0000269|PubMed:28803808, ECO:0000269|PubMed:7989588, ECO:0000269|PubMed:8499925, ECO:0000269|PubMed:8822952, ECO:0000269|PubMed:8822954, ECO:0000269|PubMed:9446754, ECO:0000269|PubMed:9856489}. The disease is caused by variants affecting the gene represented in this entry.

DB12980; DB12731; DB05217

P02792; Q01628; P03886; P43490; Q70CQ1-2

EC 2.4.2.12

3D-structure; Acetylation; Biological rhythms; Cytokine; Cytoplasm; Glycosyltransferase; Nucleus; Phosphoprotein; Proteomics identification; Pyridine nucleotide biosynthesis; Reference proteome; Secreted; Transferase

A,B

105483

932

0.11

34.4

6.68

-2.24

-7.57

HCRTR2

Homo sapiens (Human)

Ox2r; Ox2-R; Ox-2-R; Orexin-2 receptor; Hypocretin receptor type 2; HFGANP

G-protein coupled receptor 1 family

GPCR rhodopsin

Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding. Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides.

Hyperchlorhidrosis, isolated (HYCHL) [MIM:143860]: An autosomal recessive disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat. {ECO:0000269|PubMed:21035102, ECO:0000269|PubMed:21184099, ECO:0000269|PubMed:26911677}. The disease is caused by variants affecting the gene represented in this entry.

DB15031; DB11951; DB09034

P62937

NA

3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

A

32524.7

282

0.14

38.96

9.18

12.36

-7.56

NPPB

Homo sapiens (Human)

NA

NA

Natriuretic peptide family

Hormone / growth factor receptor

Diuretic hormone activity.Hormone activity.Peptide hormone receptor binding.Receptor binding.

Multiple fibroadenomas of the breast (MFAB) [MIM:615554]: A benign breast disease marked by lobuloalveolar growth with abnormally high proliferation of the epithelium, and characterized by the presence of more than 3 fibroadenomas in one breast. Fibroadenomas are adenomas containing fibrous tissue. {ECO:0000269|PubMed:18779591}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hyperprolactinemia (HPRL) [MIM:615555]: A disorder characterized by increased levels of prolactin in the blood not associated with gestation or the puerperium. HPRL may result in infertility, hypogonadism, and galactorrhea. {ECO:0000269|PubMed:24195502}. The disease is caused by variants affecting the gene represented in this entry.

DB01136; DB06412

A8MQ03; P57678; Q6A162; P60411; Q7Z3S9; P25788; Q9UJW9

NA

3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein; Hormone; Pharmaceutical; Proteoglycan; Proteomics identification; Reference proteome; Secreted; Signal; Vasoactive; Vasodilator

E

46353.1

415

0.1

37.91

5.51

-12.09

-7.56

CYP2C8

Homo sapiens (Human)

NA

NA

Cytochrome P450 family

Oxidoreductase

Arachidonic acid epoxygenase activity.Aromatase activity.Caffeine oxidase activity.Estrogen 16-alpha-hydroxylase activity.Heme binding.Iron ion binding.Monooxygenase activity.Oxygen binding.

A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions. {ECO:0000269|PubMed:2875799, ECO:0000269|PubMed:3285301}.

DB08607; DB08496; DB14055; DB12001; DB05812; DB15568; DB00918; DB12015; DB01424; DB01118; DB00321; DB00381; DB00613; DB01060; DB17449; DB01217; DB01435; DB11901; DB06605; DB00714; DB01072; DB01076; DB11995; DB00972; DB08822; DB12781; DB13997; DB05015; DB16703; DB06770; DB05229; DB00443; DB12236; DB00307; DB01393; DB13746; DB16536; DB06616; DB12267; DB12151; DB01194; DB01222; DB00921; DB06772; DB08875; DB00201; DB13919; DB00796; DB09061; DB08502; DB00564; DB00482; DB06119; DB00439; DB00608; DB00169; DB09201; DB00501; DB00604; DB12499; DB00349; DB00845; DB00758; DB00257; DB00363; DB00907; DB01394; DB05219; DB00531; DB08912; DB11682; DB00250; DB09183; DB01609; DB01234; DB14649; DB09213; DB00829; DB00586; DB00255; DB00343; DB01184; DB00625; DB11979; DB15444; DB06210; DB13874; DB11718; DB08899; DB00530; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB00402; DB00977; DB14766; DB00973; DB12466; DB04854; DB01023; DB01039; DB16165; DB00544; DB13867; DB08906; DB00588; DB01095; DB11679; DB01241; DB01645; DB11978; DB01218; DB00741; DB14538; DB14539; DB14540; DB14541; DB14542; DB14543; DB14545; DB14544; DB01611; DB12471; DB01050; DB09054; DB01181; DB00619; DB16200; DB01029; DB11633; DB06636; DB00951; DB11757; DB14568; DB09570; DB01221; DB06738; DB01026; DB01009; DB00465; DB00448; DB01259; DB09078; DB12070; DB05667; DB08918; DB00451; DB04725; DB00281; DB17083; DB01583; DB09198; DB06448; DB00836; DB00455; DB12130; DB00678; DB00227; DB09280; DB15935; DB06077; DB08932; DB14921; DB14009; DB00603; DB00784; DB00814; DB00170; DB00532; DB01357; DB00333; DB09241; DB00959; DB00916; DB01110; DB06595; DB00834; DB16236; DB11763; DB00764; DB14512; DB00471; DB00295; DB06510; DB00688; DB01024; DB00486; DB00788; DB09199; DB00622; DB00184; DB01115; DB04868; DB06712; DB12005; DB06670; DB09080; DB16267; DB12513; DB09296; DB00338; DB11632; DB01062; DB12612; DB01229; DB03796; DB05467; DB00617; DB06589; DB08922; DB00850; DB00780; DB01174; DB00946; DB00252; DB01132; DB00554; DB17472; DB08860; DB08901; DB15822; DB14631; DB00635; DB01032; DB00818; DB00205; DB04216; DB00908; DB00468; DB01129; DB00481; DB08896; DB11853; DB14761; DB00912; DB16826; DB00615; DB01045; DB11753; DB01201; DB01220; DB08864; DB08931; DB14840; DB14924; DB00503; DB09200; DB00533; DB00412; DB04847; DB12332; DB00938; DB12543; DB01232; DB00418; DB01037; DB11362; DB15685; DB11689; DB06739; DB00641; DB01261; DB00398; DB15569; DB00421; DB09118; DB00359; DB06729; DB01138; DB00675; DB00799; DB12020; DB09256; DB01079; DB12095; DB15133; DB00857; DB00342; DB08880; DB00624; DB13943; DB13944; DB13946; DB11712; DB00208; DB06137; DB01124; DB01685; DB00214; DB08911; DB00374; DB00755; DB00897; DB12245; DB12808; DB00347; DB00440; DB00197; DB13179; DB11652; DB15328; DB12255; DB15114; DB00862; DB11613; DB08881; DB00661; DB08828; DB09068; DB12026; DB00682; DB00549; DB01198

P13473-2; O75400-2; Q9Y371

1.14.14.1

3D-structure; Alternative splicing; Direct protein sequencing; Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Steroid metabolism

A

52511

463

0.1

37.03

8.6

6.74

-7.55

EGLN1

Homo sapiens (Human)

NA

PNAS-137;C1orf12;PNAS-118

NA

Oxidoreductase

Enzyme binding.Iron ion binding.L-ascorbic acid binding.Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors.Peptidyl-proline 4-dioxygenase activity.Peptidyl-proline dioxygenase activity.

Erythrocytosis, familial, 3 (ECYT3) [MIM:609820]: An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels. {ECO:0000269|PubMed:16407130, ECO:0000269|PubMed:17579185}. The disease is caused by variants affecting the gene represented in this entry.

DB00126; DB11682; DB14490; DB14491; DB14488; DB14501; DB14489; DB08687; DB01592; DB07112; DB04847; DB12255

Q99814; Q14318; Q16665; Q13438; PRO_0000037551 [Q9WMX2]

1.14.11.29

3D-structure; Acetylation; Alternative splicing; Congenital erythrocytosis; Cytoplasm; Dioxygenase; Disease variant; Iron; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; S-nitrosylation; Vitamin C; Zinc; Zinc-finger

A

24902.1

221

0.1

26.19

7.71

1.16

-7.56